The goal of the University of Texas M.D. Anderson Cancer Center SPORE in Breast Cancer is to facilitate innovative translational research in the biology, detection, prevention and treatment of breast cancer, leading eventually to elimination of this disease. Our dedicated collaborative researchers will accomplish this goal by effective integration of laboratory, epidemiologic, translational and clinical research, which will lead to changes in clinical practice that will provide innovative prevention and treatment strategies and improve outcome for patients with this disease. M.D. Anderson Cancer Center has made the elimination of breast cancer a priority by dedicating resources to establish the Breast Cancer Research Program (BCRP) whose purpose it is to support research in breast cancer. The BCRP has transcended departmental and institutional lines to form an integrated multidisciplinary research program focused on advancing the detection, diagnosis, treatment, and prevention of breast cancer. The BCRP has made it possible to recruit new investigators to the institution and to support breast cancer research of existing faculty through their support of pilot projects, strengthening the research infrastructure, and supporting new breast cancer research initiatives. The clinicians and scientists included in this application represent multiple departments and areas of expertise. They have been selected for the SPORE program because of their ongoing interest in translational research, their current level of peer-reviewed funding relevant to this application, the quality of their research, and their commitment to work together as a team. The SPORE is led by a senior clinical investigator and a senior laboratory-based researcher, includes three main areas: research, comprised of five main projects;research support, comprised of three cores;and research development, comprised of the Developmental Research Program and the Career Development Program. The three Cores (administrative, biostatistics and data management, and tissue procurement and pathology) are led by investigators with a track record of accomplishment in their chosen field. The individual Cores will provide the support that will assure the completion of the projects. The five projects that comprise the foundation of this proposal are: 1) Determinants of response to therapy and outcomes in breast cancer patients of different ethnic backgrounds 2) Cyclin E as a novel and powerful prognosticator for breast cancer 3) Treatment of metastatic breast cancer with gene modified mesenchymal stem cells 4) PTEN deficiency and trastuzumab resistance and 5) Targeting breast cancer-specific gene therapy. Each project includes both basic and clinical Co-Leaders. Thus, each project's leadership has complementary strengths and areas of expertise that will allow us to work together in the translation of new findings to clinical therapies and screening procedures.